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Published on: September 18, 2013
Adipocytes Impair Mitoxantrone Cytotoxicity Against Acute Lymphoblastic Leukemia
Michael Cohen1, Etan Orgel2,3, Jessica Nevarez-Mejia1
1Division of Pediatric Endocrinology UCLA Children's Discovery and Innovation Institute David Geffen School of Medicine University of California Los Angeles Los Angeles California USA.
Introduction:
Obesity contributes to poorer clinical outcomes in patients with acute lymphoblastic leukemia. We have shown that adipocytes cause anthracycline resistance by absorbing and metabolizing them into less-active alcohol metabolites.
Methods:
We hypothesized that mitoxantrone, which has a similar cytotoxic mechanism to anthracyclines but is metabolized through different pathways, might overcome this adipocyte-mediated chemoresistance. We treated human BV173 acute lymphoblastic leukemia cells with daunorubicin and mitoxantrone that had been incubated with or without 3T3-L1 adipocytes.
Results:
Contrary to our hypothesis, adipocytes induced similar chemoresistance to both drugs.
Conclusion:
Mitoxantrone is unlikely to be an attractive alternative to overcome adipocyte-mediated anthracycline resistance in patients with obesity.
Trial Registration:
The authors have confirmed clinical trial registration is not needed for this submission.
